1088 Part VI / The Biology of Emotion, Motivation, and Homeostasis
Figure 44–5 The REM sleep switch.Brain stem neurons are
essential for controlling the transitions between non–rapid eye
movement (REM) and REM sleep. REM sleep is generated by
a population of neurons in the rostral pons, just ventral to the
laterodorsal tegmental nucleus and locus ceruleus, in what is
called the sublaterodorsal area in rodents and the subceruleus
region in humans. These glutamatergic neurons project to
other parts of the brain stem, where they initiate the motor and
autonomic manifestations of REM sleep, and to the forebrain,
where they mediate behavioral and electroencephalographic
components of REM sleep. The descending projection activates
inhibitory interneurons in the medulla and spinal cord that pro-
foundly hyperpolarize motor neurons and prevent the individual
from acting out his or her dreams. These REM-on neurons are
inhibited by GABAergic neurons in the ventrolateral periaque-
ductal gray matter and adjacent pontine reticular formation,
while the latter are themselves inhibited by neurons
in the REM-on region, thus forming a flip-flop switch (see
Figure 44–4B). These REM-off neurons are under the control
of forebrain neurons, including neurons that release the excita-
tory orexin neuropeptides, neurons in the ventrolateral preoptic
nucleus (VLPO) that release the inhibitory signaling molecules
γ-aminobutyric acid (GABA) and galanin, and hypothalamic
neurons that release the inhibitory neuropeptide melanin-
concentrating hormone (MCH). In addition, modulatory neurons
in the locus ceruleus and dorsal raphe inhibit the REM genera-
tor, whereas cholinergic neurons in the pedunculopontine and
laterodorsal tegmental nuclei promote REM sleep. This model
explains many clinical observations, such as the fact that cho-
linergic agonist drugs promote REM sleep, whereas drugs such
as antidepressants that increase monoamine levels suppress
REM sleep. Loss of orexinergic neurons can cause abrupt
onset of REM sleep, whereas loss of REM-on neurons in the
sublaterodorsal area abolishes atonia during REM sleep. Thus,
individuals with this condition act out their dreams (REM sleep
behavior disorder).
快速眼动
开启
快速眼动
关闭
脑桥脚核
外侧被盖核
脊髓和脊髓运动
抑制性中间神经元
产生无张力
基底前脑
唤醒系统
食欲肽
腹外侧视前核
乙酰胆碱
γ-
氨基丁酸
腹外侧
中脑导水管周围灰质
γ-
氨基丁酸
蓝斑下区
γ-
氨基丁酸
谷氨酸
黑色素浓缩素
蓝斑
去甲肾上腺素
中缝背核
血清素
sleep pressure. The circadian wake-promoting signal
dips slightly in the mid-afternoon, when many peo-
ple take a nap or siesta. Around the habitual bedtime,
this circadian waking influence rapidly collapses, the
homeostatic drive for sleep is unopposed, and sleep
ensues. In the hour or two before the customary wak-
ing time, circadian promotion of sleep occurs to ensure
an adequate amount of sleep, since homeostatic sleep
pressure is low late in the sleep period (Figure 44–6A).
Circadian rhythms are driven by a small group of
GABAergic neurons in the suprachiasmatic nucleus
located in the hypothalamus just above the optic chi-
asm. The 24-hour rhythm of activity in this biological
clock is driven by a set of “clock genes,” which undergo
a transcriptional-translational cycle with an approxi-
mately 24-hour period. The positive limb of the loop
consists of two proteins, BMAL1 and CLOCK, which
dimerize and form a transcription factor that binds
to the E-box motif, which is found in the promoter
region of hundreds of genes that undergo daily cycles
in their expression. Among those genes whose expres-
sion is increased by BMAL1 and CLOCK are the Period
and Cryptochrome genes. Their protein products also
dimerize, form a complex with casein kinase 1 delta or
epsilon, and are translocated to the nucleus of the cell,
where they cause BMAL1 and CLOCK to dissociate
Kandel-Ch44_1080-1100.indd 1088 12/12/20 3:25 PM